A goal of in vivo Near Infrared Reflectance Spectroscopy [“NIRS”] is to provide a reliable and accurate noninvasive quantification of oxyhemoglobin concentration [HbO2], deoxyhemoglobin concentration [Hb], total hemoglobin concentration [HbO2+Hb] and/or tissue hemoglobin oxygen saturation [HbO2]/[HbO2+Hb] in a tissue environment where measured light photons, 650 nm to 1000 nm for example, are numerously scattered along their propagation paths. In vivo NIRS instruments use reflectance mode probes to measure scattered light remitted at some distance from where the light is emitted into the tissue. This probe spacing distance weights the measured attenuated light signal to hemoglobin absorption occurring below the tissue surface.
Continuous wave (CW) spectrometers measure changes in the attenuation of 2-6 wavelengths of light, allowing algorithms based on a modified Beer-Lambert law to provide good estimates of changes in the tissue concentration of HHb and HbO2, (measured in micromoles chromophore per ml of tissue interrogated by the NIR light). However, the ultimate goal of tissue near infrared spectroscopy is the measurement of absolute chromophore concentrations. This requires additional information. This can occasionally be gained by physiological manipulation e.g. head tilting, venous occlusion, arterial occlusion and slow or rapid changes in the inspired oxygen fraction. Under appropriate conditions these methods allow for the calculation of the flow of hemoglobin into tissue, the rate of removal of oxygen from hemoglobin and the oxygenation state of hemoglobin entering specific compartments. Suitable calculations (with relatively few a priori assumptions) can then be used to measure such physiological parameters as blood flow, blood volume, venous saturation and tissue oxygen consumption.
It is also possible to gain the additional information required to calculate absolute chromophore concentrations by the use of more sophisticated measurement systems. Time resolved (TRS) instruments use pulsed lasers with synchronized detection in order to resolve the amount of time that launched photons remain in tissue, picoseconds, before being detected. Phase resolved (PMS) instruments modulate the intensity of emitted light at a MHz frequency in order to relate a phase shift between emitted and detected signals to the average amount of time, and hence distance, that photons travel within tissue. For both methods either a time domain or frequency domain solution to a diffusion theory equation allows an estimate of the tissue absorption coefficient, μa. Once a tissue absorption coefficient is known for the wavelengths of emitted light, the concentration of the significant absorbers can be determined.
Multiple source detector separations have also been used to generate additional information. In the simplest designs two detectors are spatially separated, one close to the source (e.g. 2 cm) and one more distant (e.g. 4 cm). The assumption is then made that the additional light attenuation due to the longer separation comes only from deep tissue and that traveling the shorter path includes significant information from surface chromophores (e.g. in the skin or skull). The difference between the two then yields information about the absolute tissue chromophore concentration. Such methods (predominantly used to resolve problems in adult brain measurements) have met with only limited success. However, recently more sophisticated CW instruments have been developed using spatially resolved spectroscopy (SRS) to quantify NIRS signals representative of tissue hemoglobin oxygen saturation and total hemoglobin concentration. SRS measures an attenuated light signal at multiple probe spacing distances to solve for tissue absorption using an assumed or calibrated value for transport tissue scattering coefficient, μs′, using diffusion theory equations. Additionally, a phase resolved method has been combined with the multi-distance approach to provide a measured estimate of μs′ and estimates of tissue hemoglobin oxygen saturation and total hemoglobin concentration.
While all these methods yield apparent values for tissue chromophore concentrations, there have been relatively few attempts to compare and/or cross-validate, one against the other. The mean values of resting hemoglobin saturation can vary between methods; direct comparisons sometimes, but not always give similar readings. Tissue absorbers which exhibit non-linear absorption and overlap the measured wavelength region can confound measurement accuracy for the desired analyte. The degree of measurement inaccuracy would depend upon the relative amounts of the interfering and analyte chromophores and their characteristic absorbance magnitude at each measured wavelength (absorption coefficient).
Water has a non-linear spectral attenuation in the wavelength region of 680 to 800 nm that is amplified due to its high concentration in tissue, 70 wt % or 43 M considering lean tissue density of 1.1 Kg/L. It is desirable to limit the amount of chromophore interference (i.e. water) from an analyte chromophore measurement (i.e. % StO2).
Many publications have been devoted to measurement of tissue attributes using NIRs including, Anderson D L, Houk G L, Lewandowski M S, Myers D E and Ortner J P, Tissue chromophore measurement system, U.S. Pat. No. 5,879,294 March 1999; Binzoni T, Quaresima V, Barattelli G, Hiltbrand E, Gurke L, Terrier F, Cerretelli P and Ferrari M, Energy metabolism and interstitial fluid displacement in human gastrocnemius during short ischemic cycles, J Appl Physiol 85: 1244-51, 1998; Chance B, Cope M, Gratton E, Ramanujam N and Tromberg B, Phase measurement of light absorption and scatter in human tissue, Review of Scientific Instrumentation, 69: 3457-81, 1998; Colier W N, van Haaren N J and Oeseburg B, A comparative study of two near infrared spectrophotometers for the assessment of cerebral haemodynamics, Acta Anaesthesiol Scand Suppl 107: 101-5, 1995; Cooper C E, Elwell C E, Meek J H, Matcher S J, Wyatt J S, Cope M and Delpy D T, Noninvasive measurement of absolute cerebral deoxyhemoglobin concentration and mean optical path length in the neonatal brain by second derivative near infrared spectroscopy, The, Pediatric Res 39: 32-8, 1996; Cui W, Kumar C and Chance B, Experimental study of migration depth for the photons measured at sample surface, Proc SPIE 1431: 180-91, 1991; De Blasi R A, Fantini S, Franceschini M A, Ferrari M and Gratton E; Cerebral and muscle oxygen saturation measurement by frequency-domain near-infra-red spectrometer, Med Biol Eng Comput 33: 228-30, 1995; De Blasi R A, Ferrari M, Natali A, Conti G, Mega A and Gasparetto A, Noninvasive measurement of forearm blood flow and oxygen consumption by near-infrared spectroscopy, J Appl Physiol 76: 1388-93, 1994; Delpy D T and Cope M, Quantification in tissue near-infrared spectroscopy, Phil Trans R Soc Lond 352: 649-59, 1997; Ferrari M, Wilson D A, Hanley D F, Hartmann J F, Rogers M C and Traystman R J, Noninvasive determination of hemoglobin saturation in dogs by derivative near-infrared spectroscopy, Am J Physiol 256: H1493-9, 1989; Flessland L D, Gritsenko S I, Lewandowski M S and Myers D E, Calibration mode recognition and calibration algorithm for spectrophotometric instruments, U.S. Pat. No. 6,667,803, December 2003; Franceschini M A, Gratton E, Hueber D and Fantini S, Near-infrared absorption and scattering spectra of tissues in vivo. Pro. SPIE 3597: 526-31, 1999; Gritsenko S I, Lewandowski M S and Myers D E, Signal acquisition and processing system for reduced output signal drift in a spectrophotometric instrument, U.S. Pat. No. 6,377,840, April 2002; Gritsenko S I, Lewandowski M S, Myers D E, Quast K R and Schmidt M A Optical connector latching mechanism for a spectrophotometric instrument 6,481,899, November 2002; Hoofd L, Colier W and Oeseburg B, A modeling investigation to the possible role of myoglobin in human muscle in near infrared spectroscopy (NIRS) measurements, Adv Exp Med Biol 530: 637-43, 2003; Lefevre G, Bonneau C, Rahma S, Chanu B, Brault D, Couderc R and Etienne J, Determination of plasma protein-bound malondialdehyde by derivative spectrophotometry, Eur J Clin Chem Clin Biochem 34, 631-6, 1996; Lewandowski M S, Quast K R, Myers D E and Schmidt M A, Fiber optic light mixer, U.S. Pat. No. 6,487,343 November 2002; Matcher S J, Elwell C E, Cooper C E, Cope M and Delpy D T, Performance comparison of several published tissue near-infrared spectroscopy algorithms, Anal Biochem 227: 54-68, 1995; Mayhew J, Johnston D, Berwick J, Jones M, Coffey P and Zheng Y, Evaluation of absorption and first and second derivative spectra for simultaneous quantification of bilirubin and hemoglobin Clin. Chem. 32: 598-602, 1986; Punwani S, Ordidge R J, Cooper C E, Amess P and Clemence M, MRI measurements of cerebral deoxyhaemoglobin concentration, NMR Biomed 11: 281-9, 1998; Simpson C R, Kohl M, Essenpreis M and Cope M, Near-infrared optical properties of ex vivo human skin and subcutaneous tissues measured using the Monte Carlo inversion technique, Phys Med Biol 43: 2465-78, 1998; Skov L, Pryds O, Greisen G and Lou H, Estimation of cerebral venous saturation in newborn infants by near infrared spectroscopy, Pediatr Res 33: 52-5, 1993; Visser M, Gallagher D, Deurenberg P, Wang J, Pierson R N Jr and Heymsfield S B, Density of fat-free body mass: relationship with race, age, and level of body fatness, Am J Physiol 272: E781-7, 1997; and Yoxall C W, Weindling A M, Dawani N M H and Peart I, Measurement of cerebral venous saturation by near infrared absorption spectroscopy, Pediatr Res 36: 45 A, 1994.
Still, a need exists for a NIR instrument that reduces the effects of a confounding chromophore on the output signal value.